酪酸梭菌对乙肝相关性慢性肝病病人肠道菌群的影响

EFFECT OF CLOSTRIDIUM BUTYRICUM ON INTESTINAL FLORA IN PATIENTS WITH CHRONIC HEPATITIS B-RELATED LIVER DISEASES

目的探讨应用酪酸梭菌对乙型肝炎(乙肝)相关性慢性肝病肠道菌群的影响。方法选取2019—2020年在青岛市第六人民医院接受系统治疗且临床资料完整的慢性乙型肝炎病人53例、肝硬化病人49例和肝癌病人48例,以同期健康体检者28例作为健康对照。将慢性乙型肝炎病人、肝硬化病人、肝癌病人再分别随机分为对照组(给予常规治疗)和治疗组(在常规治疗基础上加服酪酸梭菌活菌胶囊)。对所有入选病人及健康志愿者大便菌群进行16s rDNA高通量测序和宏基因组测序,并分析其菌群多样性、丰度和酪酸梭菌含量,利用LefSe等生物信息学软件分析菌群差异。结果所有样本检测显示,拟杆菌门和厚壁菌门是肠道菌群的绝对优势菌。与健康对照相比,乙肝相关性慢性肝病病人肠道菌群中拟杆菌门所占百分比下降,厚壁菌门和放线菌门占比上升(H=8.69~13.59,P<0.05)。口服酪酸梭菌治疗后,治疗组肠道酪酸梭菌和双歧杆菌占比明显高于对照组(H=24.29、33.64,P<0.05),chao指数和ace指数较对照组显著增加(H=30.86、34.06,P<0.05)。结论口服酪酸梭菌能够改善病人肠道菌群结构,促进益生菌生长,改善肠道微生态,可能成为干预乙肝相关性慢性肝病的一种有效方法。

Objective To investigate the effect of Clostridium butyricum on intestinal flora in patients with chronic hepatitis B-related liver diseases.Methods A total of 53 patients with chronic hepatitis B,49 patients with liver cirrhosis,and 48 patients with liver cancer who received systemic therapy and had complete clinical data in Qingdao Sixth People’s Hospital from 2019 to 2020 were selected,and 28 healthy volunteers who received physical examination during the same period of time were enrolled as healthy controls.The patients with chronic hepatitis B,liver cirrhosis or liver cancer were randomly divided into control group(conventional treatment)and treatment group(Clostridium butyricum viable capsules in addition to conventional treatment).16s rDNA high-throughput sequencing and metagenomic sequencing were performed for the fecal flora of all patients and healthy volunteers to analyze the diversity and abundance of flora and the content of Clostridium butyricum,and bioinformatics software such as LefSe was used to analyze the differences in flora.Results The detection of all samples showed that Bacteroidetes and Firmicutes were the absolute dominant bacteria in intestinal flora.Compared with the healthy controls,the patients with chronic hepatitis B-related liver diseases had a significant reduction in the percentage of Bacteroidetes and significant increases in the percentages of Firmicutes and Actinobacteria in intestinal flora(H=8.69-13.59,P<0.05).After oral administration of Clostridium butyricum capsules,compared with the control group,the treatment group had significantly higher percentages of intestinal Clostridium butyricum and Bifidobacterium(H=24.29,33.64;P<0.05)and significant increases in chao index and ace index(H=30.86,34.06;P<0.05).Conclusion Oral administration of Clostridium butyricum can improve the intestinal flora structure of patients,promote the growth of probiotics,and improve intestinal microecology,and therefore,it may become an effective method for the treatment of chronic hepatitis B-related liver diseases.